Our recent work has focused upon studies of the internal motions of the HIV-1 protease (a) complexed with the potent inhibitor, DMP323, a member of a novel class of symmetric, specific and potent (Ki ~ 10-1000 pM) inhibitors in which a diol moiety is incorporated into a seven membered cyclic urea ring and (b) free in solution, as a fully active, but stable protease mutant (Q7K, L33I, L63I). The studies of the protease/DMP323 complex represent a significant extension of previous work that was made possible by our development of a novel method to study slow backbone motions in the protease, using complementary measurements of amide 15N and 1H transverse relaxation times. For this purpose we use a protein which is highly deuterated at non-exchangable hydrogen sites, and is dissolved in H2O so that the exchangable amide hydrogens are protonated. The high level of deuteration minimizes the contribution of 1H-1H dipolar interactions to the proton relaxation rate. This in turn facilitates the detection of the conformational exchange contribution to the proton relaxation rate. Measuring both the 1H and 15N transverse relaxation rates significantly increases the likely hood that relaxation due to slow conformational exchange will be detected. The new experiments clearly reveal the contribution of conformational exchange to the proton relaxation rates of residues T4, L5 and W6 in the autolysis sensitive loop. Previously, these slow motions were indirectly inferred from the absence of the L5 NH signal in our spectra. The new experiments also revealed that in the free protease, residues G48 through I54 (in the flaps of the protein) undergo slow conformation exchange. These results suggest that the flaps act as gates that open and close on the timescale of milleseconds, permitting entry and exit of ligands from the active site of the enzyme.